Process for preparing polymethine dyes



Patented Nov. 15, 1949 Edward; B: Knott, Wealdstone Eng and, assigning t: Eastman Kodak Company, Rochester;

a corporation of New Jersey N, Ya

No. Drawing-l. Applica n January 19 erial No. 573,626.. In Great Britain March This. invention relates. to .a process ..for1-prepar:- ing polymethine dyes, especially photographic sensitizing polymethine dyes, andto intermediates useful in the preparation of such dyes.

A number, of methods..,ha-Ve. been proposed for preparing symmetrical carbocyanine dyes (trimethine cyanine dyes). For certain symmetrical carbosyanine dyes, one of the mostvuseful processes involves the condensation of an orthoformic ester; inthe presence of a basic condensing agent, with'a quaternary salt of a heterocyclic nitrogen compcund hav-inga methyl group attachedto the carbon atom -in-the 2- or 4-positionto the quatennary-nitrogen atom. It is alscknown that certain symmetrical carbocyanine dyes can beprena d y; ondensing, n the pre en s a aliphatic carboxylic anhydr-ide and the alkali metal salt of an aliphatic carboxylic acid, a diarylformaniidine with a quaternary saltof aheterocyclic nitrogen compound of the aforesaid kind.-

It' is also known that equimolecular proportions ofa diarylforrnamidine and a quaternary salt" ofa heterocyclic nitrogen compound of thea-foresaidlnnd can-be condensed, in the presence oii an aliphatic carboxylic anhydride and an alkali'metalsalt of an aliphatic carboigylic acid, to give a quaternary salt of a heterocyclic nitroen: ompound; having. a cra y a ylamin rinyl; group attached to thecarbon atom in the 2- or -n n o. he quaternary nitro en a qmr I is known that these p-acylarylaminovinyl CQI1 ounds can be cond nsed; in t e pre nce Q b sic condensing, nts, th q atern sa t oiihctocy ic i gen compo nds avi a methyl group attached to the carbon atom in the 2- or four compounds, formamide is the least reactive and requires fusion at an elevated temperature, e. g. 150 to 160 0., preferably employing the alkyl toluenesulfonate of' the nitrogen base. Thioformanilide reacts-with'the quaternary salts readi y. n alkal ne; media. as. pyrid ne. .9; i

8 -Claimsr (01.260-240) ce ic t acet c anhrdride conta nin alkal metal a tate-.. 'lih o rmam sic r act best n l a n alcqhqliqm'edia, ef. a, a1.v h cw istnvlsmir c r odiumethyla e. rd maznidoxinie reacts e t in, A .nh drisi ntainin wi illdill a e t h. fasy idil or riet y smiu 1,1 hus bos es h t a Wide Variety Of n.- ciensing agsntsmay hous d ohelisi qluw tion o alkal hydroxid 'c floi l organic bases, such as pyridinefp'iperidine,

methylamine, triethylamine or their alcoholic QllJJZiQ ;-;@llr1ji al a is, YQFQXiQE 9. carbonates, or condensing agents, such as acetic anhydride containing sodium acetate. The most suitable condensing agent for any particular quaternary saltcan; readily bev ascertained by the customary obseryationsanddepends to a considerable extent, as indicatedabovaupon wheths i ormamide, iotqtmam d hiqt rmsnilide o n amidox me is emp oye In Pl a k ol ens u tcnat s Ima u othe uate na a ts s s a a ky ha d s or allgyl sulfates, as well as the corresponding aralkyl quat rna y s l 'i' Iherea ion ake n ac bst een wo m ecu s.

Qfi't e qu terna a n n m ecu e of he orm m qai h fQr id h q rman l s o formamidoxime, but itis not essential in allcases to bring the reagents intov contact in these proportions-althoughJitis preferredlto doso. It has vbeen ,obseryed, however, and this constitutes a further feature of the invention, that inter-v medi es co si ting, o fiac amido yl om-.. pounds are obtained when substantially equimolecular proportions are used and. when the condensing agent. is acetic anhydridaprovided al o that f he. her reagent is t iof m mid he qu terna y. salt s. a a ky ha d o i he other reagent is formami o me th erna y salt is not an alkyl halide. With formamide or ormamid xime t se nterm diatesare o med event iromthe alkyl paratoluenesulfonates or alk l s ni ts hrfqrma i m alkyl p r toluenesulfonates are. preierred, Thioforrnans ilide, howevendoes not give such intermediates.

These ,B-acetamidovinyl "inter-mediates are usem for m ki g carbosra ne dyes by condens ies with. sterosys ic; ni r gen uat nary salts a in ams hyl gr up attached o m c a atom in the. 2 or l position to the quaternary nitrogen atom, such as quinaldine or lepidine quaternary salts; 0r-iormaking merocarbccyanine dyes by condensation with compounds ayin setsme h le gr ans.

th -quat rnary saltsiemployedg ay s de ived Example I.--3:3-dimethylthiocarbocyanine iodide 2 -meth ylbenzthiaz ole metho-p-toluenesulfonate (3.35 g.) and thioformamide (0.33 g.) dissolved in ethyl alcohol (30 cc.) were refluxed to dissolve and triethylamine (0.5 cc.) added and the mixture refluxed for 30 minutes. The deep red solution was poured into aqueous potassium iodide and the required dye collected and recrystallized from methanol in the form of coppery needles giving a red solution in alcohol. Yield 66 per cent.

Example II.3:3-dimethylcarbocyanine iodide Quinaldine metho-p-toluenesulfonate (3.29 g.) and thioformamide (0.33 g.) were dissolved in ethyl alcohol (75 cc.) and triethylamine (0.5 cc.) added; on refluxing further a thick meal of the required toluenesulfonate separated. This was collected, dissolved in alcohol and the iodide precipitated by pouring into aqueous potassium iodide. 'Recrystallized from methanol, it formed green needles giving a pure blue solution in alcohol. Yield 58 per cent.

Example I I I .3 :3 -diethylcarbcyanine iodide As for Example II, using quinaldine etho-ptoluenesulfonate (3.45 g.) gave a 45 per cent yield of green needles after recrystallization from methanol.

Example IV.3:3'-diethylcarboeyanine iodide Quinaldine etho-p-toluenesulfonate (3.43 g.) and formamide (0.25 g.) were fused at 160 C. for one hour. The clear melt slowly turned blue and partially solidified to a mass of green crystals. These were collected, Washed with a little acetone, dissolved in alcohol and poured into aqueous potassium iodide. The required iodide was then recrystallized from methanol.

Example V.--3:3-diethylcarbocyanine iodide Quinaldine ethiodide (2.99 g.) and thioformanilide (1.37 g.) were refluxed in pyridine (50 cc.) for 1 hour. lized from methanol as green needles.

Example VI .-3 :3'-dimethylthiocarbocyanine v iodide 2-methylbenzthiazole metho-p-toluene sulfonate (3.29 g.) and thioformanilide (1.37 g.) were The dye was collected and recrystal- F t refluxed in acetic anhydride cc.) and an= hydrous sodium acetate (0.82 g.) for 30 minutes. The acetic anhydride was removed under reduced pressure and the dye taken up in alcohol and poured into aqueous potassium iodide.

Example VII.-2-pl-acetamidovinylquinoline ethiodide Quinaldine ethiodide (2.99 g.) and thioformamide (0.67 g.) were refluxed in acetic anhydride (100 cc.) for 45 minutes and allowed to cool. The crystalline precipitate was collected and recrystallized from alcohol. It then formed pale brown needles, M. P. 258 C. Yield 2.4 g.

Example VIII.--2-p-acetamidovinylbenzthiazole ethiodide N (12 Ht \I 2-methylbenzthiazole ethiodide (3.05 g.), thicformamide (0.67 g.) and acetic anhydride (12 cc.) \were refluxed for 45 minutes. A red color developed which slowly faded. After cooling, the solid was collected and recrystallized from alcohol forming pale brown needles, M. P. 240 to 241 C.

Example IX.-2 ,3 acetamidovinylbenzoxazole ethiodide 2-methylbenzoxazole ethiodide (2.99 g.), thioformamide (0.67 g.) and acetic anhydride (10 cc.) were heated at 100 C. on the water bath for 1 hour. The required substance was precipitated as an orange oil by adding ether. The ether was decanted and a few drops of alcohol added to the oil which crystallized. Recrystallized from a little alcohol, it formed fiat pink needles M. P. 216 to 217 C.

Example X.-2-p acetamidooinylqainoline ethiodide Quinaldine etho-p-toluenesulfonate (3.43 g.), formamide (0.45 g.) and acetic anhydride (15 cc.) were refluxed for 1 hour, acetic acid (5 cc.) was added and the mixture poured into aqueous potassium iodide. The required iodide separated as pale brown needles. Yield 3.2 g. M. P. 359 C.

Example XI.2 6-acetamidovinylquinoline ethiodide Quinaldine ethiodide (2.99 g.), iormamide (0.45 g.) acetic anhydride (100 cc.) were refluxed for 45 minutes and allowed to cool. The needles which separated were recrystallized from alcohol M. P. 258 C.

Example XII.2-p acetamidovinylbenzthiazole ethiodide 2-methylbenzthiazole ethiodide (3.05 g.), formamide (0.45 g.) and acetic anhydride cc.) were refluxed for 45 minutes and allowed to cool. The reddish needles were recrystallized from 8.1- cohol and had M. P. 240 C.

Example XIII .--2-B acetamidovinylbenzoxazole ethiodide 2-methylbenzoxazole ethiodide (2.89 g.) formamide (0.45: g.) and acetic anhydride(10cc;:): were; refluxed ,for 30- minutes, thev required substance precipitated by adding ether and the oil crystallized. from methanol M. B. .217. 0..

Ewample XV.-2 B acetamioZovin/ lbemethiacole cthiodz'de Proceeding as above and using 2-methylbenzthiazole etho-p-toluenesulfonate (3.49 g.), the required substance was obtained as reddish crystals M. P. 240 to 241 C.

Example XVI.-2-p acetamidovinylbenzowaeole ethoperchlorate 2-methylbenzoxazole etho-p toluenesulfonate (3.33 g.) formamidoxime (0.60 g.) and acetic anhydride (5 cc.) were refluxed for 15 minutes, the acetic anhydride removed in vacuo and the residue dissolved in water (5 cc.) This solution was then poured into a saturated solution of sodium perchlorate. On standing overnight, the required substance separated. It was recrystallized from boiling water and formed beautiful, long, pale orange, glassy needles M. P. 181 -to 183 C. containing water of crystallization,

' The e-acetamidovinyl compoundsprepared in accordance with my invention can be condensed with compounds containing a ketomethylene (CO-CH2) or a thioketomethylene (CS-CH2) group, in the presence of a basic condensing agent, to give merocarbocyanine dyes. In British Patent 432,628, accepted July 23, 1935, the preparation of merocyanine dyes using p-acetamidovinyl compounds is proposed. However, no examples are given in that patent, the examples provided always involving the use of a p-acetanilidovinyl compound. The basic condensing agent proposed in the British patent is pyridine.

I have found, however, that by using alkali metal or alkaline earth metal hydroxides or carbonates or alcoholates, as the condensing agent, much higher yields can be obtained than are obtained when pyridine is used as the basic condensing agent in connection with p-acetamidovinyl compounds. Often, yields of 50 or 60 per cent can be obtained. On the other hand, with pyridine as the basic condensing agent, it is extremely difiicult to get yields of more than a few per cent.

The compound having a methylene group adjacent to a carbonyl or thiocarbonyl group may be an open chain compound or a cyclic compound, especially a heterocyclic compound. Examples of open chain compounds which may be used are ethyl-2-quinolyl pyruvate, acetylacetone, acetoacetamides, cyanoacetamides and benzoylacetonitrile. Examples of cyclic compounds are thiazolones (such as isothiohydantoin) thiazolidones,

a: lones. 1,3-cyclohexandiones, .2,4.-,dihydroxyquinclines, oxydihydroquincxalines, dihydr.ocarhosty-v rils, coumaranones, oxindoles, ketodihydrobenze parathiazines benzo-p-morpholones, homo. phthalimide and succinimidaindanedione, tete ronic acid, ketodihydrothionaphthenes such as thioindoxyl, and indoxyls.

The. following examples illustratedhow. the .invention may be practiced.

Example XVII .3 ethyl 5 -(3-ethyl- 2 'bcnzomazyZidene-ethylidene) I-phengl- 2 thiohydantoin II-cam 2-;8--acetamidovinylbenzoxazole ethiodide (358 mg. .001 mol. 1-phenyl-3 ethyl-2-thiohydantoin- 222' mg. .001 mol.) were dissolved in ethyl alcohol-(2.5 cc.) and'a solution of sodium- (23 mg.) in alcohol (1 cc.) added to the mixture of 40 C. Thedye began-crystallizing at once. It was collected-after chilling and recrystallized from spirit in orange needles.

Example XVIII.-.3-ethyl.-5.-(I-thykZ-quinoZyL wane-ethylidene) rhodcm'ne 2 13-acetamidoyinylquinoline ethiodide (36.8 mg, .001 mol.) and3-ethyl rhodanine (161 mg., .001

" mol.) were dissolved in alcohol (5 cc.) and a solution of potassium hydroxide (56 mg.) in ethyl alcohol (5 cc.) added at 60 C. The required dye separated after a short time. It formed bluish grey crystals giving a purple alcoholic solution.

Other dyes which may be made in the manner of the foregoing examples are:

3 ethyl 5 (3 ethyl 2 benzthiazylideneethylidene) l-phenyl-Z-thiohydantoin 3 -ethyl 5 (1 ethyl 2 quinolylidene ethylidene) 1-phenyl-2-thiohydantoin 3 ethyl 5 (3 ethyl 2 benzoxazylideneethylidene) -rhodanine 3 ethyl 5 (3 ethyl 2 benzthiazylideneethylidene) -rhodanine 5 (3 ethyl 1 benzoxazylidene ethylidene)- 1 :3-diphenyl-rhodanine 5 (3 ethyl 1 benzthiazylidene ethylidene)- 1 :3-diphenylrhodanine 5 (1 ethyl 2 quinolylidene ethylidene)- 1 3-diphenylrhodanine What I claim as my invention and desire to be secured by Letters Patent of the United States 1. A process for preparing a carbocyanine dye comprising condensing one molecular proportion of a compound selected from the group consisting of formamide, thioformamide, thioformanilide and formamidoxime, with two molecular proportions of a quaternary salt of a heterocyclic nitrogen base containing a methyl group attached to the carbon atom in the position selected from the group consisting of the 2- and the 4-positions.

'2. A process for preparing a carbocyanine dye comprising condensing by heating one molecular proportion of a compound selected from the group consisting of formamide, thioformamide, thioformanilide and formamidoxime, with two molecular proportions of a quaternary salt of a heterocyclic nitrogen base containing a methyl group attached to the carbon atom in the position selected from the group consisting of the 2- and 4-positions.

H 3. A process for preparing a carbocyanine dye comprising fusing one molecular proportion of formamide with two molecular proportions of a quaternary salt of a heterocyclic nitrogen base containing a methyl group attached to the carbon atom in the position selected from the roup consisting of the 2- and 4-positions.

4. A process for preparing a carbocyanine dye comprising fusing one molecular proportion of formamide with two molecular proportions of a quaternary alkyl toluene sulfonate of a heterocyclic nitrogen base containing a methyl group attached to the carbon atom in the position selected from the group consisting of the 2- and 4-positions.

5. A process for preparing a carbocyanine dye comprising condensing, in the presence of an acid-binding agent, one molecular proportion of thioformanilide with two molecular proportions of a quaternary salt of a heterocyclic nitrogen base containing a methyl group attached to the carbon atom in the position selected from the group consisting of the 2- and ii-positions.

6. A process for preparin a carbocyanine dye comprising condensing, in the presence of acetic anhydride and an alkali metal acetate, on molecular proportion of thioformanilide with two molecular proportions of a quaternary salt of a heterocyclic nitrogen base containing a methyl group attached to the carbon atom in the'position selected from the group consisting of the 2- and 4-positions.

7. A process for preparing a carbocyanine dye comprising condensing, in the presence of an acid-binding agent, one molecular proportion of thioformamide with two molecular proportions of a quaternary salt of a heterocyclic nitrogen base containing a methyl group attached to the carbon atom in the position selected from the group consisting of the 2- and Jr-positions.

8. A process for preparing a carbocyanine dye comprising condensing, in the presence of an alkaline-alcoholic acid-binding agent, one molecular proportion of thioiormamide with two molecular proportions of a quaternary salt of a heterocyclic nitrogen base containing a methyl group attached to the carbon atom in the position selected from the group consisting of the 2- and -positions.

EDWARD B. KNOTT.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS OTHER REFERENCES,

Sidgwick, Organic Chemistry of the Nitrogen Compounds; page 151. 

